Oxidative stress and acute phase response were assessed in post-transition early-lactation and mid-lactation Holstein cows regards to the possible effects on milk production and reproductive performance. In two farms, 113 cows, 2-6 years old within 21-150 days in milk (DIM) were sampled for whole blood three times with 30-day intervals. The concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), haptoglobin (Hp) and serum amyloid A (SAA) were measured in plasma. Three DIM stages were defined for further comparisons: DIM=21-70 as a post-transition early-lactation; 71-110 as the late weeks of early-lactation and the early weeks of mid-lactation; and 111-150 as the major portion of mid-lactation. Blood parameters (DIM=21-150) of the cows that conceived before (n=29) and after (n=56) DIM=110 and the cows that remained open (n=27) were also compared with the same test. The relationships between blood parameters (DIM=21-150) and performance indices were studied by Spearman’s rho correlation test. The studied performance records were not statistically different (P>0.05) between farms and between the cows that conceived (n=85) and the cows that remained open (n=27). GPx was not different (P>0.05) among DIM stages in the sum of both farms, though it increased significantly in Farm 2 at DIM=111-150. The levels of SOD and MDA were not different between farms and among DIM stages (P>0.05). The levels of Hp and SAA through DIM stages were close to or higher than those reported in fresh or diseased cows and their changes were mostly not significant. Performance records and blood parameters were not different (P>0.05) between the cows that conceived before DIM=110 or later and those that remained open. Negative correlations were observed between Hp and the maximum milk yield of the first 90 days (r=-0.20, P=0.034) and average milk yield during 150 DIM (r=-0.17, P=0.065). No relationship was observed between the plasma parameters and the studied reproductive records. The activity of GPx showed negative correlations with the level of Hp (r=-0.14, P=0.036) and the activity of SOD (r=-0.19, P=0.004). Oxidative stress was not a problem of the studied farms during DIM=21-150. However, high levels of Hp and SAA could reveal continuous mild stressful or inflammatory conditions during DIM=21-150, contributing to the less efficient milk production.